You need to get calories from somewhere, should it be from carbohydrate or fat?

Saturday, October 20, 2012

Protons: Love your superoxide (outside your brain)

Two off topic posts in a day! How come? I had the weirdest morning today. A three hour consulting session with only six appointments, all straight forward. Bloody hell, was I lucky for a Saturday! Can't blog at work so I had a quick browse to see what Nick Lane has been up to recently. He has a cracking article up (as a pdf) on heteroplasmy which rewards careful reading in its own right, but look at these two "throw away" quotes.

How do we minimise mitochondrial biogenesis? By running metabolism on glucose of course, but don't forget the lack of superoxide generation when oxidising PUFA. But who needs mitochondria when you can lower LDL levels by swilling corn oil? Ah cardiology, you have a lot to answer for. Executive summary: Want mitochondria? Burn PALIMTATE.

And on cerebral metabolism:

"In the brain, where further mtDNA biogenesis is limited, neurons would then become compromised whenever energy demands were high, possibly causing acute cognitive and behavioral abnormalities".

The brain neurons are running on lactate under crapinabag conditions. We considered this before. No fatty acids. No glycerol 3 phosphate. No FADH2 input to the CoQ couple. No free radicals. No signal for mitochondrial biogenesis. No mitochondrial biogenesis. You could substitute ketones and maybe get a few mitochondria back if you were canny, but most medics aren't canny. What happens to the lactate supply for neurons when hyperglycaemia drops on to chronically elevated FFAs and triggers apoptosis in glial cells? I think we can attach various labels, depending on which neuronal cell types die first. Alzheimers seems a nice name for the commonest scenario.

Lovely pair of quotes. Glad I got the browse time. But don't ignore the heteroplasmy discussion at the core of the article, it's good stuff.

8 comments:

This is a topic that seems to leave me with ever more questions. A bit of background..

Mitochondria are probably from a swallowed up symbiotic relationship of the past - which ended up as an cellular organelle.

Mitochondria, have asexual reproduction which lacks the haploid diploid benefits of sexual evolution's shuffling of traits followed by a fitness run of the haploid generation.

There is this bit: on the female haploid side, the eggs are protected - not exposed to the stresses. This story seems incomplete to me.

Asexual reproduction needs lots of repetition to get the fittest, but mitochondria are locked into cells and can't be exchanged as best as I know.

There was something about some gene repair of mitochondria via the nucleus of the cell - not sure how well we know this.

Eventually, there is going to be enough non repairable genetic damage of mitochondria in the average cell that that ends up with cells that need destruction. Some don't get destroyed and end up as senescent cells that leak interluekins and generally muck things up.

What this bit has me thinking about is that at times of low mitochondria numbers, the cell is more at risk of losing a healthy copy of mitochondrial DNA thus more likely to become a senescent cell.

This paper seems to point out there is some reason for maintaining a mono-culture of mitochondria - Perhaps preventing male mitochondria from having a role? (Which reminds me of the paper that suggests that some 60% of women that have had children have some of the fathers DNA in their brain.. just really strange http://dx.plos.org/10.1371/journal.pone.0045592

And there is also a recent finding that sperm contain a large amount of RNA in sperm that may have some important effect on reproduction ( part of the proof of viability? ).

http://www.sciencedirect.com/science/article/pii/S0093691X07003068

There may be some biological battle of the sexes at play in all these cases.)

I wonder if this would help explain a gradual increase in athletic performance I have experienced since adapting to a VLCKD and avoiding PUFA as far as practicable?

As a confounder I have lost some weight as well but was pretty lean to start with.

In the back of my mind I did wonder what would happen if I re-introduced regular anaerobic sprints into my training as a mitochondrial stimulus. That's an n=1 experiment I might try when fully back into maintenance mode calorie-wise.

Now of course the question of dietary/supplementary antioxidants comes in to play here. can I assume it's mostly water soluble anti-ox's doing the cellular ROS scavenging in this context?

I regularly take a time-release multi-vit which, like these things do, contains 2.5x The RDA for Vit C. Now as much as I don't want scurvy I also don't like the idea of inhibiting mitochondrial biogenesis if it's going to do me some good.

So what's a boy to do? probably give up the expensive pill habit and just eat real food? I'm guessing the requirement for B vitamins is much reduced on a VLC diet anyway and am probably doing OK for fat soluble vits from diet as it is - although will prob stick to taking supplemental vit D

Cracking paper. Over feeding produces fat gain in exact ptoportion to carb intake. Keep the carbs constant and you can exchange fat for protein and get identical fat gain. It's the carbs that matter (at a quick read). Bray is such an idiot. Read the results, I doubt it is even worth skimming the discussion (I haven't)

Peter

O Num, I pay the price for portable stearic acid (100gm of 90% cocoa chocolate) by accepting a ton of flavanoids from the cocoa. I rely heavily on my liver to dump these antioxidants as fast as possible! I also doubt a couple of hundred mg of ascorbate does much harm...

My daily stimulant is a cup of green or black tea. These types of drinks increase thermogenesis in the short term. But the longer term effect could be to decrease mitochondrial production of atp, and hence overall energy production.

If i kicked this habit do you think i might find that my overall energy levels rise after my mitochondria get a chance to respond to this increased ROS signalling? I went the first 17 years of my life without caffeine or any other stimulants after all. Had tons of energy back then!

This question of whether antioxidants are good or not seems very intersting to me. Some people are starting to say that the types of antioxidants are very important, and that more is not necessarily always better.

Im including a reference to a paper (below) that seems to show, with "compelling" evidence, that induction of the β-adrenoceptor (β-AR) signaling pathway for Mitochondrial Biogenesis leads to activation of multiple genes involved in the mitochondrial electron transport chain, increased mtDNA copy number, and increased respiratory capacity, at least in the hearts and kidneys of the cats that they tested on.

If free radicals emanating from mitochondria acts as a signal to the nuclear genome to increase MB, or to destroy damaged mitochondria, then anti oxidants are only going to disrupt this process.

About Me

I am Petro Dobromylskyj, always known as Peter. I'm a vet, trained at the RVC, London University. I was fortunate enough to intercalate a BSc degree in physiology in to my veterinary degree. I was even more fortunate to study under Patrick Wall at UCH, who set me on course to become a veterinary anaesthetist, mostly working on acute pain control. That led to the Certificate then Diploma in Veterinary Anaesthesia and enough publications to allow me to enter the European College of Veterinary Anaesthesia and Analgesia as a de facto founding member. Anaesthesia teaches you a lot. Basic science is combined with the occasional need to act rapidly. Wrong decisions can reward you with catastrophe in seconds. Thinking is mandatory.
I stumbled on to nutrition completely by accident. Once you have been taught to think, it's hard to stop. I think about lots of things. These are some of them.

Organisation (or lack of it)!

The "labels" function on this blog has been used to function as an index and I've tended to group similar subjects together by using labels starting with identical text. If they're numbered within a similar label, start with (1). The archive is predominantly to show the posts I've put up in the last month, if people want to keep track of recent goings on. I might change it to the previous week if I ever get to time to put up enough posts in a week to justify it. That seems to be the best I can do within the limits of this blogging software!